Ishikawa Y, Takagi Y, Takeno H, Watanabe K, Tani T
New Drug Research Department, Sumitomo Metal Industries, Kyoto, Japan.
Biol Pharm Bull. 1998 Sep;21(9):928-33. doi: 10.1248/bpb.21.928.
The hypoglycemic effect of the novel oral agent 3-[4-12-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-phenyl]-2S-propyla mino-propionic acid (HQL-975) was examined in db/db mice with genetically obese non-insulin dependent diabetes mellitus (NIDDM). The oral administration of HQL-975 at 3.5 and 35.3 mg/kg/d for 7 d decreased the plasma glucose level of these mice in a dose-dependent manner. HQL-975 also significantly decreased the plasma triglyceride, total cholesterol, non-esterified fatty acid and insulin levels. In the oral glucose tolerance test, HQL-975-treated mice showed improved glucose tolerance and decreased endogenous insulin secretion. HQL-975 increased glycemic response to exogenous insulin in the mice. In the HQL-975-treated db/db mice adipocytes, the glucose uptake, insulin binding, and GLUT4 expression were increased compared with those in untreated db/db mice adipocytes. These results indicate that HQL-975 improved insulin action in db/db mice through receptor and post-receptor effects. In conclusion, HQL-975 is a new oral antidiabetic agent with a hypoglycemic effect which is associated with an insulin-sensitizing effect. This agent may therefore be effective for the treatment of NIDDM.
在遗传性肥胖非胰岛素依赖型糖尿病（NIDDM）的db/db小鼠中检测了新型口服药物3-[4-12-(5-甲基-2-苯基-恶唑-4-基)-乙氧基]-苯基]-2S-丙氨基丙酸（HQL-975）的降血糖作用。以3.5和35.3mg/kg/d的剂量口服HQL-975，持续7天，可使这些小鼠的血糖水平呈剂量依赖性降低。HQL-975还显著降低了血浆甘油三酯、总胆固醇、非酯化脂肪酸和胰岛素水平。在口服葡萄糖耐量试验中，经HQL-975治疗的小鼠表现出葡萄糖耐量改善，内源性胰岛素分泌减少。HQL-975增加了小鼠对外源性胰岛素的血糖反应。在经HQL-975治疗的db/db小鼠脂肪细胞中，与未治疗的db/db小鼠脂肪细胞相比，葡萄糖摄取、胰岛素结合和GLUT4表达增加。这些结果表明，HQL-975通过受体和受体后效应改善了db/db小鼠的胰岛素作用。总之，HQL-975是一种新型口服抗糖尿病药物，具有降血糖作用，且与胰岛素增敏作用相关。因此，该药物可能对NIDDM的治疗有效。
